Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Australia.
Mult Scler. 2013 Apr;19(4):385-91. doi: 10.1177/1352458512463769. Epub 2012 Oct 16.
Ion channel dysfunction is an important mechanism that contributes to functional disability and axonal degeneration in multiple sclerosis (MS). Recent studies have revealed that there are complex rearrangements of voltage-gated Na(+) channels that occur with acute brain inflammation in MS, with up-regulation of primitive Na(+) channel isoforms such as Nav 1.2 during acute inflammation. While these changes may help support neural conduction, increased expression of 'persistent' Na(+) conductances and altered function of the Na(+)/K(+) pump may contribute to axonal degeneration in MS. Increased expression of K(+) channels due to demyelination has also been considered as a contributing factor to conduction failure in MS. Recent phase II and phase III clinical trials have demonstrated improvements in walking speed in patients receiving fampridine SR, a K(+) channel blocker. This medication appears to be well-tolerated with a low risk of serious adverse events and provides benefits in both relapsing and progressive forms of MS.
离子通道功能障碍是导致多发性硬化症（MS）功能障碍和轴突变性的重要机制。最近的研究表明，在 MS 的急性脑炎症中，存在电压门控 Na(+)通道的复杂重排，在急性炎症期间，原始 Na(+)通道亚型如 Nav 1.2 的表达上调。虽然这些变化可能有助于支持神经传导，但“持续”Na(+)电导的表达增加和 Na(+)/K(+)泵功能的改变可能导致 MS 中的轴突变性。脱髓鞘导致的 K(+)通道表达增加也被认为是 MS 中传导失败的一个促成因素。最近的 II 期和 III 期临床试验表明，接受 fampridine SR（一种 K(+)通道阻滞剂）治疗的患者的步行速度有所改善。这种药物耐受性良好，严重不良事件的风险低，并为复发型和进行型 MS 提供益处。
